Nu-alkoxy amides of 4-halophenoxyalkylcarboxy acids



United States Patent Cfifice assasar Patented Nov. 14, 196'? 3,352,897 N-ALKOXY AMIDES F 4-HALOPHENOXY- ALKYLQARBOXY ACHD$ Sidney B. Richter, Chicago, 11]., assignor to Velsicol Chemical Corporation, Chicago, lib, a corporation of Illinois No Drawing. Filed Apr. 10, 1963, Ser. No. 271,869 The portion of the term of the patent subsequent to Feb. 2, 1982, has been diselaimed 14 Claims. (Cl. 260-453) This invention relates to the control of undesirable pests. More specifically, this invention relates to the control of undesirable plant life, particularly crabgrass.

It has now been found that undesirable plant life can be controlled very effectively with the use of chemical compounds which are N-mono-alkoxy amides of 4-halophenoxy alkyl mono-carboxy acids. These new chemical compounds have the structural formula wherein X is a halogen atom, R is selected from the group consisting of hydrogen, and substituted and unsubstituted alkyl groups, R is selected from the group consisting of substituted and unsubstituted alkyl groups, and Z is an unsubstituted alkylene group containing from one to four carbon atoms. In a preferred embodiment of this invention, Z is as described above, X is selected from the group consisting of chlorine, bromine, iodine and fluorine, R is selected from the group consisting of hydrogen and unsubstituted alkyl groups containing from one to ten carbon atoms, and R is an unsubstituted alkyl group containing from one to ten carbon atoms.

The novel alkoxy amides of the present invention can be prepared conveniently from the corresponding acid, which is often commercially available, or can be synthesized by treating the corresponding 4-halophenol with an alkali metal hydroxide to form the salt, and treating the salt with a bromo-alkyl acid of the formula wherein Z is as described above, or a lower alkyl ester of the acid and then hydroiyzing. Alternatively, free acids, other than 4-halophenoxy-acetic acids can be prepared from the corresponding 4-halophenoxyalkyl acid wherein Z has one less CH group attached to the COOH group than in the desired free acid, by reducing the lower acid with lithium aluminum hydride at a low temperature, treating the resulting alcohol with thionyl chloride to obtain the halide, treating the halide with sodium cyanide and then hydrolyzing theh product to obtain the free acid.

Examples of the free acids from which the compounds of the present invention can be prepared, are: 4-chlorophenoxy-acetic acid, 4-bromopl1enoxy-acetic acid, 4-iodophenoxy-acetic acid, 4-fluorophenoxy-acetic acid, cz-(4- chlorophenoxy) propionic acid, 5 (4 chlorophenoxy)- propionic acid, ot-(4-chlorophenoxy)-n-buty1ic acid, fl-(4- chlorophenoxy)-n-butyric acid, 'y-(4-chlorophenoxy)-n butyric acid, ot-(4-chlorophenoxy)-iso-butyric acid, 'y-(4- chlorophenoxy)-n-valeric acid, 5-(4-chlorophenoxy) -nvaleric acid, a-(4-bromophenoxy)-propionic acid, 06-(4- iodophenoxy)-propionic acid, 06-(4 fiuorophenoxy)-pro pionic acid, 8-(4-bromophenoxy)-propionic acid, 'y (4- bromophenoxy)-n-butyric acid, and the like.

The free acid can then be converted to its acid chloride, which is treated with an alkoxyamine of the formula wherein R and R are as described above, to give the desired compound of the present invention. Suitable amines of the above formula can be prepared, for example, by the reduction of the corresponding oximes as described by Jones and Major, J. Am. Chem. Soc., vol. 52, pp. 669-79 (1930). Exemplary of suitable alkoxy amines useful as a reactant to prepare the N-alkoxy amides of the present invention, are: N-methoxy-amine, N-methoxy- N-methylamine, N-ethoxyamine, N-ethoxy N methylamine, N-ethoxy-N-ethylamine, N-methoxy N ethylamine, N-n-propoxyamine, N-iso-propoxyamine, N-npropoxy-N-ethylamine, and the like.

More particularly, the free acid is treated with an equimolecular or greater quantity of thionyl chloride, preferably in a solvent or diluent, such as benzene. An amount of solvent or diluent approximately equal in volume to the volume of the free acid has been found to be satisfactory. The treatment is performed by heating for several hours, preferably at reflux if a solvent or diluent, such as benzene, or large excess of thionyl chloride is used. The corresponding acyl chloride thus formed can be isolated from the reaction mixture by means common to the art, such as by distillation of the solvent or diluent and unreacted reactants, leaving the acyl chloride as the residue.

In the second step, the acyl chloride is reacted with an equimolecular or greater amount of the appropriate N-alkoxyamine or preferably its hydrochloride, in the presence of a base, such as sodium hydroxide, potassium hydroxide and potassium carbonate. At least one equivalent quantity of base, is used when the free amine is utilized as the reactant, and at least twice that amount is used when the amine hydrochloride is used as the re actant. The base is used to release the amine from its hydrochloride, and to neutralize the hydrogen chloride, formed during the reaction. A small amount of water is preferably added to the reaction mixture to form an aqueous solution of the base to aid in mixing the base into the solution of the amine or amine-hydrochloride reactant. The reaction is conveniently performed utilizing a solvent or diluent, such as benzene, by heating for several hours preferably at reflux temperature when a solvent or diluent is used. When potassium carbonate is used as the base, completion of the reaction can be readily detected by the cessation of the release of carbon dioxide gas. The N-alkoxy amide compound of the present invention formed by the above procedure can be separated from the reaction mixture by means common to the art, such as by filtration from precipitated salts and unreacted amine, drying the filtrate and distilling the filtrate under reduced pressure to remove unreacted reactants and solvent or diluent, if used,"and to recover the desired product as the residue. The N-alkoxy amide compounds of the present invention thus obtained can be used for many applications as such, or can be recrystallized from a suitable solvent.

The manner in which the new compounds of this in vention can be prepared is illustrated in the following examples.

4-chlorophenoxyacetic acid (37.3 g.;

0.20 mol) and benzene ml.) were placed into a 300 ml., threenecked, round-bottom flask fitted with a mechanical stirrer, reflux condenser, and a dropping funnel. The contents of the flask were stirred and thionyl chloride (16 ml., 0.22 mol) was slowly added to the flask. The contents were heated to reflux, and stirring was continued at reflux for 7 hours. The reaction mixture was dried over magnesium sulfate, filtered and distilled under reduced pressure to remove benzene and unreacted thionyl chloride. The yellow liquid residue was distilled in vacuo to yield the product 4-chlorophenoxyacetyl chloride, as a clear colorless liquid boiling at 82-86 C. at 0.4 mm. mercury pressure.

Example 2.Preparati0n of N-metlzoxy-N-methyl 4-chloroplzenoxyacetamide N methoxy N methylamine-hydrochloride (8.6 g.; 0.088 mol), potassium carbonate (13.4 g.; 0.097 mol), benzene (100 ml.) and water (10 ml.) were placed in a 300-ml., three-necked, round-bottom flask, equipped with a mechanical stirrer, reflux condenser, and dropping funnel. The mixture was stirred, and 4-chlorophenoxyacetyl chloride (18 g.; 0.088 mol), prepared in Example 1, was slowly added to the flask. The addition was exothermic, and the mixture was thereafter stirred at reflux for about 7 hours. The reaction mixture was filtered and the solids Washed thrice with benzene. The benzene washings were combined, dried over magnesium sulfate, filtered, and the filtrate distilled under reduced pressure to remove benzene and to yield the product N-methoxy-N-methyl-4- chlorophenoxy-acetamide, as a clear colorless liquid boiling at 140 C. at 0.5 mm. mercury pressure, which solidified on cooling to a white solid having the following elemental analysis:

Calculated for C H ClN O -Theoretical, percent: C, 52.29; H, 5.23; Cl, 15.47; N, 6.10. Found, percent: C, 52.27; H, 5.44; Cl, 15.56; N, 6.05.

Example 3.Pr,eparazi0n of N-methoxy-4- chlorophenoxyacetamide Methoxyamine-hydrochloride (7.4 g.; 0.089 mol), potassium carbonate (13.5 g.; 0.098 mol), benzene (100 ml.) and water (10 ml.) were placed in a 300 ml. threenecked, round-bottom flask fitted with a mechanical stirrer, reflux condenser and dropping funnel. The mixture was stirred, and 4-chlorophenoxyacety1 chloride (18.3 g.; 0.089 mol), prepared in Example 1, was slowly added to the flask. The addition was exothermic, and the mixture was thereafter stirred at reflux for about 7 hours. The reaction mixture was filtered and the solids collected. The filtrate therefrom was dried over magnesium sulfate,.filtered, and the filtrate therefrom distilled under reduced pressure to remove benzene to yield a white solid residue which was added to the previously collected solids and the mixture recrystallized from benzene, washed with pentane, and dried to yield white solid N-methoxy 4-chlorophenoxy-acetamide, melting 105.5108 C. and having the following elemental analysis:

Calculated for C H C1NO -Theoretica1, percent: C, 50.12; H, 4.64; Cl, 16.47; N, 6.5. Found, percent: C, 50.26; H, 4.44; Cl, 16.45; N, 6.22.

Example 4 .-Preparation of N -ethoxy-4-chlorophenoxyacetamz'de The product of Example 1 is reacted with ethoxyamine hydrochloride according to the technique of Example 3 to yield N-ethoxy-4-chlorophenoxyacetamide.

Example 5 .Preparation of N-n-propoxy-N-methyla-(4-chlor0phenoxy)-propionamide a-(4-chlorophenoxy)-propionic acid, which can be prepared by treating p-chlorophenol with sodium hydroxide and then a-bromopropionic acid, is treated with thionyl chloride. by the procedure of Example 1 to obtain a-(4- chlorophenoxy)-propionyl chloride. This latter intermediate is reacted with N-n-propoxy-N-methylamine hydroall) 4 chloride by the technique of Example 2 to yield the desired product N n propoxy N methyl a (4-chlorophenoxy)-propionamide.

Example 6.--Preparation 0f N-metlzoxy-a-(4-br0m0- phen0xy)-n-butyramide a-(4-bromophenoxy)-n-butyric acid, which can be prepared by treating 4-bromopheno1 with sodium hydroxide and then a-bromo-n-butyric acid, is treated with thionyl chloride by the procedure of Example 1 to obtain a-(4- bromophenoxy)-n-butyryl chloride. This intermediate is reacted with methoxyamine-hydrochloride according to the technique of Example 3 to yield the desired product Nmethoxy-a-(4-bromophenoxy)n-butyramide.

Example 7.--Preparati0n of N-etlzoxy-N-ethyl-fi-(lchloro plzenoxy -n-valeramid e 8-(4-chlorophenoxy)-n-valeric acid, which can be prepared by treating 4-chlorophenolwit-h sodium hydroxide, and then E-bromo-n-valeric acid, is treated with thionyl chloride by the method of Example 1 to obtain 6-(4- chlorophenoxy)-n-valeryl chloride. This intermediate is reacted with N-ethoxy-N-ethylamine-hydrochloride according to the procedure of Example 2 to yield the desired product N ethoxy-N-ethyl-fi-(4-chlorophenoxy)-nvaleramide.

Other compounds within the scope of the present invention can be prepared in the manner detailed in the previous examples. Given in Examples 8-24 are the free acid and the amine reactants which can be used to prepare the indicated named compounds of this invention.

Example 8 18-(4-chlorophenoxy)-n-butyric acid+N-rnethoxy-N-nbutylamine N methoxy N n butyl t8 (4 chlorophenoxy)-n-butyramide.

Example 9 a-(4-chlorophenoxy)-iso-butyric acid+N-ethoxy-N-npropylamine N ethoxy N n propyl a (4 ch10- rophenoxy)-iso-butyramide.

Example 10 8 (4 chlorophenoxy) n propionic acid N methoxy N methylarnine N methoxy N methyl ,6- (4-ch1orophenoxy)-n-propionamide.

Example 11 4 fluorophenoxyacetic acid n butoxyamine N- n-butoxy-4-fluorophenoxyacetamide.

Example 12 oz (4 brornophenoxy) n valeric acid 4- N methoxy. N methylamine N methoxy N methyl Ot- (4-bromophenoxy) -n-valeramide.

Example 13 4 iodophenoxyacetic acid N met-boxyamine N- methoxy-4-iodophenoxyacetamide.

Example 14 4 bromophenoxy-acetic acid N methoxy N methylamine N methoxy N methyl 4 bromophenoxyacetamide.

Example 15 or (4 fluorophenoxy) propionic acid N methoxy- N methylamine N methoxy N 4 methyl a (4 fluorophenoxy)-propionamide.-

Example 16 y 4 chlorophenoxy) n butyric acid 4- N methoxy N methylamine N methoxy N methyl 'y- (4-chlorophenoxy)-n-butyramide.

Example 17 ,8 (4 iodophenoxy) propionic acid N methoxy- N methylamine N methoxy N methyl 18 (4- iodophenoxy)-propionamide.

Example 18 a (4 chlorophenoxy) iso butyric acid N methoxy N methylamine N methoxy N methyl a- (4-chlorophenoxy) -iso-butyramide.

Example 19 4 bromophenoxyacetic acid N methoxyamine N methoxy-4-bromophenoxy-acetamide.

Example 20 c (4 chlorophenoxy) propionic acid N methovy N methylamine N methoxy N methyl Ot- (4-chlorophenoxy) -propionamide.

Example 21 a (4 chlorophenoxy) n butyric acid N methoxy N methylamine N methoxy N methyl a- (4-chlorophenoxy)-n-butyramide.

Example 22 a (4 bromophenoxy) propionic acid N methoxy N methylamine N methoxy N methyl u- (4-bromophenoxy) -propionamide.

Example 23 4 iodophenoxyacetic acid N methoxy N methylamine N methoxy N methyl 4 iodophenoxyacetamide.

Example 24 4 fiuorophenoxyacetic acid N methoxyamine N- methoxy-4-fluorophenoxyacetamide.

For practical use as herbicides, the compounds of this invention are generally incorporated into herbicidal compositions which comprise an inert carrier and a herbicidally toxic amount of such a compound. Such herbicidal compositions, which are usually known in the art as formulations, enable the active compound to be applied conveniently to the site of the weed infestation in any desired quantity. These compositions can be solids such as dusts, granules, or Wettable powders; or they can be liquids such as solutions or emulsifiable concentrates.

For example, dusts can be prepared by grinding and blending the active compound with a solid inert carrier such as the tales, clays, silicas, pyrophyllite, and the like. Granular formulations can be prepared by impregnating the compound, usually dissolved in a suitable solvent, on to and into granulated carriers such as the attapulgites or the vermiculites, usually of a particle size range of from about 0.3 to 1.5 mm. Wettable powders, which can be dispersed in water to any desired concentration of the active compound, can be prepared by incorporating wetting agents into concentrated dust compositions.

In some cases the active compounds are sufiiciently soluble in common organic solvents such as kerosene or xylene so that they can be used directly as solutions in these solvents. However, preferred liquid herbicidal compositions are emulsifiable concentrates, which comprise an active compound according to this invention and as the inert carrier, a solvent and an emulsifier. Such emulsifiable concentrates can be diluted with water to any desired concentration of active compound for application as sprays to the site of the weed infestation. The emulsifiers most commonly used in these concentrates are nonionic or mixtures of nonionic with anionic surface-active agents.

A typical herbicidal composition according to this invention is illustrated by the following example, in which the quantities are in parts by weight.

Example 25.Preparati0n of a dust Product of Example 2 10 Powdered talc The above ingredients are mixed in a mechanical grinder-blender and are ground until a homogeneous, free-flowing dust of the desired particle size is obtained. This dust is suitable for direct application to the site of the weed infestation.

The herbicides of this invention can be applied in any manner recognized by the art. The concentration of the new compounds of this invention in the herbicidal compositions will vary greatly with the type of formulation and the purpose for which it is designed, but generally the herbicidal compositions will comprise from about 0.05 to about percent by weight of the active compounds of this invention. In a preferred embodiment of this invention, the herbicidal compositions will comprise from about 5 to about 75 percent by weight of the active compound. The compositions can also comprise such additional substances as other pesticides, Spreaders, adhesives, stickers, fertilizers, activators, synergists, and the like.

Weeds are undesirable plants in their growing where they are not wanted, having no economic value, and interfering with the production of cultivated crops or with the welfare of livestock. Many types of weeds are known, including annuals such as pigweed, lambsquarters, yellow foxtail, crabgrass, wild mustard, French-weed, rye-grass, goose-grass, chickweed, and smartweed; biennials such as wild carrot, great burdock, mullein, round-leaved mallow, blue thistle, bull thistle, hounds-tongue, moth mullein, and purple star thistle; or perennials such as White cockle, perennial rye-grass, quackgrass, Johnson grass, Canada thistle, hedge bindweed, Bermuda grass, sheep sorrel, field chickweed, and winter-cress. Similarly, such weeds can be classified as broad-leaf or grassy weeds. It is economically desirable to control the growth of such weeds without damaging beneficial plants or livestock.

The new compounds of this invention are particularly valuable for weed control because they are toxic to many species and groups of weeds while they are relatively nontoxic to many beneficial plants. These new compounds are also unexpectedly and unusually effective in controlling undesirable plant growth in that they possess herbicidal activity in both the liquid and vapor phases and thus provide enhanced herbicidal action upon seeds prior to germination, particularly when the vapor is released beneath the surface of the soil, and upon seedlings after emergence from the soil by liquid phase treatment.

The method of this invention for the control of weeds comprises applying to the site of the weed infestation, and particularly to the soil containing weed seeds and seedlings, a herbicidal composition comprising an inert carrier and as the essential active ingredient, in a quantity which is herbicidally toxic to said weed seeds and/or seedlings, a compound of this invention. Application of the herbicidal composition is preferably made to the soil at or before the time of planting or between planting and the emergence of desirable plants. Where the soil is to be treated between planting and emergence of desirable plants, it is preferred to plant the seeds of desirable plants below the zone of the weed seeds. The exact amount of compound required will depend on a variety of factors, including the hardiness of the particular weed species, weather, method of application, the kind of beneficial plant seeds in the same area, and the like. Thus, while the application of up to only about one or two ounces of an active compound per acre may be sufiicient for good control of a light infestation of weeds under adverse conditions, the application of one pound or more of active compound per acre may be required for good control of a dense infestation of hardy weed seeds under favorable conditions.

The herbicidal toxicity of the new compounds of this invention can be illustrated by many of the established testing techniques known to the art. For example, emulsifiable concentrate compositions can water to concentrations equivalent to 4 pounds of the active compound per acre. Duplicate paper pots filled with a sand and soil mixture are seeded with Weeds; and immediately after seeding, the soil surface of each potis sprayed with an appropriately diluted test solution. The weed growth is maintained under artificial lighting with irrigation provided by placing the porous pots in a small amount of water in stainless steel trays. The weeds are observed for a week to ten days; and the percent kill, injury, and standreduction are recorded. The results indicate a high order of pre-emergence herbicidal activity of the compounds of this invention. Comparable preplanting tests can also be used.

The herbicidal activity of the compound of the present invention was illustrated, for example, by a number of experiments carried out for the pro-emergence control of crabgrass. Crabgrass is a term used to describe a group of summer annuals which cause extensive damage to lawns, turf, and other grassy areas. The crabgrass kills by taking moisture and nutrients from the soil and thus smothering and choking the desirable grasses. The grasses around each crabgrass plant are usually killed or seriously weakened. When the crabgrass dies, it leaves bare spots, liberally sprinkled with enough seeds to provide serious infestation the next season. The two species of crabgrass which are the most widespread weed pests of lawns are Digitaria ischaemum, commonly known as smooth crabgrass, and Digitarl'a sanguinalis, usually known as common, large, hairy, tall, purple, fingergrass, turkeyfoot, crowfoot grass, and watergrass. At least, fifteen other varieties of Digitaria species of crabgrass are known. Also generally classified with crabgrass are such weeds as goosegrass (Eleusine indica), broomsedge (Alzdropogon virginicus), pigeon grass or green bristle grass (Setaria virin'is), yellow bristle grass (Setaria lutescens), watergrass (Echinochloa crusgalli), witchgrass (Punicum capillare), cheatgrass or chess (Bromus secalinus), and downy bromegrass (Bromus tectorum).

In one series of tests, filter paper was dipped in acetone solutions of the test compounds at various concentrations. The paper was then dried, and small pieces were placed on the'bottom of plastic dishes having a film of agar nutrient and a row of crabgrass seeds set apart from the treated filter paper. The seeds were allowed to germinate under controlled laboratory conditions, and the toxicity of the chemical compounds was determined on the basis of the primary root length of the germinated seedlings, shortroot lengths being indicative of high toxicity to crabgrass. The results of these tests are summarized in the following table:

Primary root lengths in mm. at concns. in p.p.m.of Test Chemical N-rncthoxyN-metliyl-4 chlorophenoxyacetamide (Product of Example 2) l 1 2 3 3 6 l0 I3 16 UntreatedCheck 31 31 31 31 31 31 31 31 31 be diluted with placed on a greenhouse bench, watered daily or more frequently when required, and provided with supple.- mentary light and heat as needed. These conditions were maintained throughout the test.

The plants were observed on the 20th day after treatment for the type and severity of injury to each weed as compared with untreated controls. The severity of the injury was rated on a scale from 0 to 10, wherein 0 was designated for no injury to the weed and 10 was designated for total death of the weed.

The results of these tests are presented in the following tables:

TAB LE I.F OXTAIL 1 Concentration in lbs. actual test chemical per acre.

TABLE IL-HU STARD Test Chemical Concu. Injury Type of Injury Rating Product of Example ,2. 4 7 Reduced germination,

Stunting. D 0 a 8 9 D 0. Control. 0 0 None.

1 Concentration in lbs. actual test chemical per acre.

A series of post-emergence tests were performed to illustrate. the post-emergence herbicidal effectiveness of the compounds of this invention. In these tests weeds were grown in pots until they were sufficiently established and the first true leaves were fully developed. The pots were then placed on the moving table described above and the foliage of the weeds were sprayed with aqueous suspensions of the test compounds at various concentrations through the spray apparatus previously described. The pots were placed on a greenhouse bench and the soil was watered daily or more often as required. Water was not applied to the foliage of the Weeds.

The weeds were observed for the type and severity of injury as compared with untreated control weed plants, on the 13th day after treatment. The severity of the injury was rated on a scale from 0 to ,10, wherein 0 was designated for no injury to the weed and 10 was designated for total death of the weed.

The results of these tests are presented in the tables below:

TABLE TIL-MUSTARD Test Chemical Concn. Injury Type of Injury Rating Product of Example 2- 4 9 Epinasty, general necrosis. Do 8 10 General necrosis. Control 0 0 None.

1 Concentration in lbs. actual test chemical per acre.

TABLE IV.PIGWEED 1 Concentration in lbs. actual test chemical per acre,

9 I claim: 1. A compound of the formula f, O--Z-( 3-N \OR H H wherein X is a halogen atom, R is selected from the group consisting of hydrogen and unsubstituted alkyl groups containing from one to ten carbon atoms, R is an unsubstituted alkyl group containing from one to ten carbon atoms, and Z is an unsubstituted alkylene group containing from one to four carbon atoms. N-rnethoXy-4-ch1orophenoxyacetamide. N-methoxy-N-methyl-4-chlorophenoxyacetamide. N-ethoxy-4-chlorophenoxyacetamide. N-rnethoxy-4-bromophenoxyacetamide. N-methoxy-N-methyl-4-bromophenoxyacetamide. N-methoxy-N-methyl u (4ch1orophenoxy) propionamide.

8. N-methoxy-N-methyl a (4-ch1orophenoXy)-nbutyramide.

(4-chlorophenoxy) -iso- References Cited UNITED STATES PATENTS 2,723,192 11/1955 Todd 71---2.6 2,726,150 12/1955 Welter 71-2.6 2,911,440 11/1959 Thullier et a1. 260559 3,027,407 3/ 1962 Major et a1. 260-559 3,168,561 2/1965 Richter 260-559 OTHER REFERENCES Eckstein et a1.: Chemical Abstracts, vol. 51, page 8695 1957 Thompson et al.: Botanical Gazette, 476-486 (1946).

JOHN D. RANDOLPH, Primary Examiner. NICHOLAS RIZZO, WALTER MODANCE, Examiners.

R. PRICE, N. TROUSOF, Assistant Examiners.

vol. 107, pages 

1. A COMPOUND OF THE FORMULA 